Hot flashes (HFs) currently affect approximately 35 million women in the U.S. Recent results from the Women's Health Initiative showed that, for many women, the risks of HRT outweigh the benefits and it use has rapidly declined. Thus, there is a great need for research on the underlying mechanisms of HFs and for new treatments for them. Our HF theory posits that HFs are triggered by small elevations in core body temperature (Tc) acting within a reduced thermoneutral zone in symptomatic women. A critical test of this theory would be to rapidly lower Tc and determine if HFs are ameliorated. A new device (Core Control) may accomplish this and, in Study 1, we will test to determine if it significantly lowers Tc and ameliorates HFs in symptomatic postmenopausal women. Controlled studies have shown that relaxation-based procedures, such as paced respiration, are efficacious in the treatment of HFs. However, these methods are unavailable to many women. Therefore, in Study 2, we propose to test the efficacy of a home training device vs. the effects of a plausible behavioral placebo and simple instructions and to determine if paced respiration training exerts its effects by raising the Tc sweating threshold. Work thus far suggests that elevated levels of brain norepinephrine (NE) play a role in the initiation of HFs, and that NE and serotonin (5 HT) work in opposition in thermoregulation. Acute tryptophan depletion has been shown to reduce brain 5 HT, so we will test to see if it lowers the Tc sweating threshold (Study 3). If decreased brain 5 HT increases HFs, then elevated 5 HT should ameliorate them. We propose to test the efficacy of an SSRI using objective physiological methods, and determine the time course and mechanism of its effect upon HFs (Study 4) These studies are relevant to public health because hot flashes are a troublesome symptom for millions of women and optimal treatments are currently lacking. [unreadable] [unreadable] [unreadable]